Freeze-drying tray assembly

Abstract

Disclosed herein are assemblies, systems, and methods for preventing contamination and alteration of biological materials during and after lyophilization. A tray assembly configured to retain a biological material in a container during a freeze-drying process, the tray assembly including a tray and a complementary lid. The lid may include a compressible leg member configured to transition from an extended configuration to a compressed configuration in response to a downward force applied on the lid when the lid is positioned over the tray. When the supporting leg components extend, a gap exists between the upper edge of the tray and the bottom face of the cover body. And under the condition that the supporting legs extend and the tray assembly is opened, the tray assembly is freeze-dried. After lyophilization is completed, the legs may be compressed and the lid may be sealed over the tray, thereby enclosing the biological material within the assembly and protecting it from contamination inside and outside the chamber and exposure to ambient air.

Description

[0001] Cross - reference to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 476,258, filed on December 20, 2022, the entire content of which is incorporated herein by reference. Technical Field

[0003] This application relates to a component, system, and method for performing operations such as freeze - drying and packaging of materials under aseptic or pathogen - reduced conditions. Background Art

[0004] Dry storage can extend the shelf life of biological materials and improve their ease of use. Freeze - drying (or lyophilization) is a process for drying heat - sensitive substances (such as biological materials) by freezing the substance and then sublimating ice or other frozen solvents in a high - vacuum environment.

[0005] To avoid decomposition of the material and prevent possible infections when using the material, it is necessary to ensure that biological materials are protected from microorganisms and other contaminants. During the transportation of biological materials to a freeze - dryer for freeze - drying or from the freeze - dryer, the biological materials may be exposed to contaminants and undesirable atmospheric conditions. Therefore, the operating area for freeze - drying requires frequent sterilization to minimize the risk of biological materials being exposed to contaminants and ambient air. This increases the manpower and costs associated with freeze - drying operations.

[0006] Many freeze - drying processes involve placing open containers containing biological materials in a freeze - dryer. These containers remain open to the environment throughout the freeze - drying process so that solvent vapors can escape from the biological materials. This practice exposes the biological materials to potential contamination risks, especially when the freeze - dryer is opened after the freeze - drying process is completed. To minimize the risks of contamination and unnecessary air exposure during and after the freeze - drying process, the freeze - drying equipment can be sterilized using steam or chemical reagents before each new batch of biological materials to be processed is loaded. This also increases the manpower and costs associated with freeze - drying.

[0007] In addition, using existing components, systems, and methods, some freeze - dried biological materials may need to be repackaged after drying. This repackaging provides an opportunity for contaminants to be introduced into the biological materials and further increases the manpower and costs associated with freeze - drying. Summary of the Invention

[0008] The present inventors recognize that, among other things, there is a current and pressing need for new components, systems, and methods to address issues of material contamination and air exposure during and after the lyophilization process, including aspects such as lyophilization equipment, the area surrounding the lyophilization equipment, and the repackaging of lyophilized products. The inventors recognize that biological materials, such as plasma, are at risk of contamination each time they are exposed to the environment. The present inventors also recognize that the components, systems, and methods should be economical and practical at the production scale.

[0009] The present disclosure provides components, systems, and methods for protecting biological materials from contamination and uncontrolled atmospheric conditions, including steps such as filling, lyophilizing, packaging, storing, and using. The system can include a lyophilization tray assembly configured to receive one or more containers, each containing a biological material, such as plasma. The container can include a flexible container similar or identical to those shown and described in U.S. Patent No. 9,561,893, the entire content of which is incorporated herein by reference.

[0010] A method can include inserting the biological material into a container before lyophilization and placing the container in a lyophilization tray. The lyophilization tray can be coupled to a complementary lid having one or more compressible members, such as leg members each in an extended configuration, such that when the lid is coupled to the tray, there is a gap between the two components. When the gap exists, the biological material can be lyophilized in the tray assembly. After lyophilization is complete, the biological material can be sealed within the tray assembly by compressing the compressible members (collectively referred to herein as "leg members") and forcing the lid against the tray. The lyophilization chamber can be opened and the enclosed tray assembly can be removed therefrom, with the container enclosed within the assembly, at which time the lyophilization conditions can be maintained and the container can be protected from contamination and exposure to an uncontrolled atmospheric environment that could compromise the state and integrity of the lyophilized material.

[0011] To further illustrate the components, systems, and methods disclosed herein, the following is a non-limiting list of examples:

[0012] In Example 1, the lyophilization tray assembly can include a tray configured to receive one or more containers, each containing a liquid. The assembly can also include a lid complementary to the tray and including one or more compressible members configured to transition from an extended configuration to a compressed configuration in response to a downward force applied to the lid when the lid is positioned above the tray. When the one or more compressible members are in the extended configuration, there can be a gap between the upper edge of the tray and the bottom surface of the lid. When the one or more compressible members are in the compressed configuration, the lid can seal against the upper edge of the tray.

[0013] In Example 2, the components of Example 1 are optionally configured such that: the components further include a gasket attached to the upper edge of the tray.

[0014] In Example 3, the components of any one of Examples 1 or 2 are optionally configured such that: the tray includes one or more partition plates configured to define two or more cavities within the tray, and each cavity is configured to receive at least one container.

[0015] In Example 4, the components of Example 3 are optionally configured such that: the partition plates are movable within the tray.

[0016] In Example 5, the components of any one or any combination of Examples 1 to 4 are optionally configured such that: each of the compressible members includes a compressible leg member having a first portion and a second portion, and the first portion is movable relative to the second portion.

[0017] In Example 6, the components of Example 5 are optionally configured such that: the first portion includes a telescopic positioning pin member.

[0018] In Example 7, the components of Example 6 are optionally configured such that: the second portion includes a tubular member configured to receive the telescopic positioning pin member.

[0019] In Example 8, the components of Example 7 are optionally configured such that: the tubular member is attached to the bottom surface of the lid, and the telescopic positioning pin member is configured to extend to the inner bottom surface of the tray.

[0020] In Example 9, the components of Example 8 are optionally configured such that: the support base of the telescopic positioning pin member is configured to contact the inner bottom surface of the tray.

[0021] In Example 10, the components of any one or any combination of Examples 1 to 9 are optionally configured such that: the tray and the lid include stainless steel.

[0022] In Example 11, the components of any one or any combination of Examples 1 to 10 are optionally configured such that: the components further include a vent attached to the tray.

[0023] In Example 12, the components of any one or any combination of Examples 1 to 11 are optionally configured such that: the tray has a length of about 20 inches to about 40 inches.

[0024] In Example 13, the components of any one or any combination of Examples 1 to 12 are optionally configured such that: the tray has a width of about 8 inches to about 20 inches.

[0025] In Example 14, the components of any one or any combination of Examples 1 to 13 are optionally configured such that: the tray has a height of about 1 inch to about 5 inches.

[0026] In Example 15, a system for freeze-drying biological materials may include: at least one airtight container configured to hold the biological materials; and a tray assembly configured to hold at least one airtight container. The tray assembly may include a tray configured to hold at least one airtight container. The tray assembly may further include a lid that is complementary to the tray and includes one or more compressible members configured to transition from an extended configuration to a compressed configuration in response to a downward force applied to the lid when the lid is positioned above the tray. When the one or more compressible members are in the extended configuration, there may be a gap between the upper edge of the tray and the bottom surface of the lid. When the one or more compressible members are in the compressed configuration, the lid may seal against the upper edge of the tray.

[0027] In Example 16, the system of Example 15 is optionally configured to further include a movable freeze-dryer shelf.

[0028] In Example 17, the system of Example 16 is optionally configured such that the movable freeze-dryer shelf is configured to apply a downward force to the lid sufficient to seal the lid against the upper edge of the tray.

[0029] In Example 18, the system of any one or any combination of Examples 15 to 17 is optionally configured such that the tray assembly further includes a vent.

[0030] In Example 19, the system of any one or any combination of Examples 15 to 18 is optionally configured such that the biological material includes plasma.

[0031] In Example 20, the system of any one or any combination of Examples 15 to 19 is optionally configured such that each of the one or more compressible members includes a compressible leg member.

[0032] In Example 21, a method for freeze-drying and processing biological materials may include placing an airtight container filled with biological materials in a cavity defined by a tray of a tray assembly. The method may further include positioning a lid complementary to the tray above the tray such that compressible members protruding from the bottom surface of the lid extend into the cavity and there is a gap between the upper edge of the tray and the bottom surface of the lid. The method may further include freeze-drying the tray assembly in a freeze-drying chamber, compressing the compressible members by applying a downward force to the lid until the gap between the upper edge of the tray and the bottom surface of the lid closes, and then removing the tray assembly from the freeze-drying chamber.

[0033] In Example 22, the method of Example 21 is optionally configured such that the downward force applied to the lid includes lowering a freeze-dryer shelf positioned above the lid so that it abuts the lid.

[0034] In Example 23, the method of any one of Examples 21 or 22 is optionally configured such that the biological material includes plasma.

[0035] In Example 24, the method of any one or any combination of Examples 21 to 23 is optionally configured such that the compressible member includes a compressible leg member.

[0036] These and other examples and purposes of the present component, system and method will be set forth in the following detailed description. This summary is intended to provide non-limiting examples of the present application and is not intended to provide an exclusive or exhaustive explanation. The following detailed description is intended to provide further information about the present component, system and method. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] In the drawings, the same reference numerals may be used to describe the same features and components in different drawings. These drawings generally illustrate, by way of example and not limitation, the various embodiments discussed in the present application.

[0038] Figure 1A A exploded view of a lyophilization tray assembly constructed in accordance with at least one embodiment is shown.

[0039] Figure 1B Shows Figure 1A A plan view of the lyophilization tray assembly shown.

[0040] Figure 1C Shows Figure 1A A side view of the lyophilization tray assembly shown in an open configuration.

[0041] Figure 1D Shows Figure 1C A side view of the lyophilization tray assembly in an open configuration, wherein the lyophilization shelf is positioned above the assembly.

[0042] Figure 1E Shows Figure 1A The bottom surface of the lid of the lyophilization tray assembly shown.

[0043] Figure 2A A tray of a lyophilization tray assembly constructed in accordance with at least one embodiment is shown, the tray including a plurality of partition plates.

[0044] Figure 2B Shows Figure 2A The tray shown, which does not include partition plates.

[0045] Figure 2C Shows Figure 2A One of the partition plates shown.

[0046] Figure 2D Shows Figure 2A The lid of the lyophilization tray assembly shown.

[0047] Figure 2E ShowsFigure 2A The leg member of the freeze-dried tray assembly shown in

[0048] Figure 3 The tray of the freeze-dried tray assembly constructed according to at least one embodiment is shown.

[0049] Figure 4A A freeze-dried tray assembly including a vent constructed according to at least one embodiment is shown.

[0050] Figure 4B Shown Figure 4A A close-up view of the vent shown therein.

[0051] Figure 5 A method of freeze-drying and preventing contamination of biological materials according to at least one embodiment is shown.

[0052] The drawings are not necessarily drawn to scale. Some features and components may be shown at an enlarged scale or in schematic form, and some details may not be shown for clarity and conciseness. Detailed Description

[0053] This application relates to a freeze-drying tray assembly and associated systems and methods of use, which are designed to protect materials from contamination and uncontrolled atmospheric conditions through steps such as filling, freeze-drying, packaging, and storage. The materials may include biological materials (such as plasma), which may be vulnerable to harmful contamination. Examples of the method may include inserting the biological material into a container and placing the container in the tray assembly. The tray assembly may include: a tray that defines one or more cavities configured to receive the container; and a complementary lid configured to couple to the tray in an adjustable manner to switch the tray assembly between an open configuration and a closed configuration. In the open configuration, uncompressed members (such as uncompressed leg members) extend from the bottom surface of the lid into the tray, and there is a gap between the upper edge of the tray and the bottom surface of the lid. The tray assembly can be placed in a freeze-drying chamber, and the freeze-drying process can be initiated with the tray assembly in the open configuration so that air and solvent vapor are discharged from the container through the gap during the process. After freeze-drying is complete, the leg members are compressed by pushing the lid towards the top edge of the tray (where the container has been sealed and optionally locked within the tray), causing the tray assembly to switch to the closed configuration. The container filled with freeze-dried material sealed within the tray assembly can be moved or otherwise handled inside or outside the freeze-drying chamber without being exposed to air and associated contamination risks. In addition to minimizing the risk of contamination, the sealed tray assembly can maintain a controlled environment therein, such as having a specific gas content (e.g., nitrogen content), temperature, and / or humidity level established during the freeze-drying process, which does not exist in the ambient atmosphere surrounding the freeze-drying chamber. Maintaining the desired atmospheric conditions within the tray assembly can prevent degradation and / or alteration of the freeze-dried material caused by air, thereby maintaining its integrity and extending its shelf life.

[0054] The method can be performed using the components and systems shown in the figures and described herein. The system provides a practical and reusable freeze-drying tray assembly configured to accommodate one or more containers during the freeze-drying process and seal the containers after freeze-drying, thereby minimizing container exposure to contaminants and maintaining a controlled atmospheric condition within the assembly after freeze-drying is complete.

[0055] Figure 1A An exploded view of a tray assembly 100 is shown, which is configured to receive and enclose a plurality of containers, each of which is configured to contain a material, such as plasma from one or more donors. For ease of explanation, "material" and "biological material" may be used interchangeably herein.

[0056] The tray assembly 100 includes a lid 102 and a complementary tray 104, the tray 104 including one or more cavities 106 defined by partitions or dividers 108 positioned within a peripheral wall 110 of the tray 104, each cavity 106 configured to receive at least one container 111. The peripheral wall 110 may include two end portions 110a and two side portions 110b that respectively define a width W and a length L of the tray 104. Other suitable geometries are also within the scope of the present disclosure. A sealing member 112 (such as a gasket, O-ring, or washer) may be secured to the top of the peripheral wall 110, where the sealing member may be sandwiched between the tray 104 and the lid 102 when the lid is pressed against the tray (such as after lyophilization) to assist in sealing the container 111 within the closed assembly. One or more adjustable leg elements 114 may be secured or attached to the lid 102 such that when the lid 102 is coupled with the tray 104, each leg member 114 projects into one of the cavities 106 defined by the tray 104. Alternatively, the leg members 114 may be attached to the tray 104, or attached to both the lid 102 and the tray 104 simultaneously, or not attached to either. The length of each leg member 114 in an uncompressed configuration may be greater than the depth of the tray 104 such that there remains a vertical gap between the lid 102 and the tray 104 after the lid 102 and the tray 104 are coupled but before sealing. The compressible leg members 114 of the present disclosure include an adjustable structure of any suitable shape or configuration. The leg members 114 may be adjustable, for example, foldable, compressible, or telescoping, such that when the lid 102 is pressed against the tray 104, the length of the leg members 114 may be shortened to eliminate the gap between the two components. In some embodiments, the leg members 114 may be integrally formed or fixedly connected to the bottom surface of the lid 102 such that the leg members 114 may be considered part of the lid 102.

[0057] Figure 1A The illustrated tray 104 includes dividers 108, which in this example, four dividers define five cavities 106. The size and structure of each cavity 106 are designed to receive at least one container 111. The embodiments are not limited to five cavities 106, and the number of cavities 106 may be one, two, three, four, five, six, seven, or more. The orientation and number of the dividers 108 may also vary and may be adjustable. For example, one or more dividers 108 may be added or removed to accommodate different numbers and sizes of containers 111 placed within the tray 104 in a particular lyophilization process.

[0058] The number of containers 111 placed in a single tray 104 can range from one to about ten or more, including two, three, four, five, six, seven, eight, nine, or more containers 111. In some embodiments, multiple containers 111 can be placed within a single cavity 106, depending on the size of the two components. Non-limiting examples of the container 111 can have a length LC of about 6 to 18 inches (e.g., about 12 inches) and a width WC of about 3 to 9 inches (e.g., about 6 inches). By being configured to accommodate multiple containers 111 at once, the tray 104 can be well-suited for efficiently batch-drying biological materials without the need for a specific container mechanism to prevent contamination and exposure to an uncontrolled atmospheric environment, as well as without the frequent decontamination of freeze dryers common in existing systems.

[0059] In embodiments employing flexible containers 111 or bags, each container can include at least one membrane 113 configured to allow air or solvent vapor to escape and prevent liquids and contaminants from entering the flexible container 111. According to such examples, each container 111 can be placed in the cavity 106 of the tray 104 with the membrane 113 facing up and towards the bottom surface of the lid 102. The size of the membrane 113 can vary, depending in part on the size of the container 111. Non-limiting examples of the membrane 113 can have a length of about 1 to 3 inches (e.g., about 2 inches) and a width of about 2 to 4 inches (e.g., about 3 inches). The material of the membrane is selected based on a combination of its high sterile barrier properties, high resistance to liquid water penetration and wetting, and low solvent vapor flow resistance. Examples include sterile paper, woven or non-woven polymer fabrics (such as spunbond polyolefins), polymer membranes (such as polytetrafluoroethylene (PTFE) and expanded polytetrafluoroethylene (ePTFE)), fiberglass, cellulose nitrate, mixed cellulose esters, polyvinylidene fluoride (PVDF), polyethersulfone, polycarbonate, nylon, polypropylene, and PVC. PTFE can be used because of its property of combining hydrophobicity and solvent vapor mobility at a given nominal pore size.

[0060] Thanks to the presence of the tray assembly 100 and its unique configuration, the container 111 can dispense with a detachable lid or other components for protecting the membrane 113 during pre- and post-freeze-drying processes. The structure of the tray assembly 100 can also support multiple containers 111 for the freeze-drying process, which can or cannot contain protective structures such as membranes.

[0061] The flexible container 111 can include a sealable material made of an inert medical-grade plastic material, such as polyvinyl chloride (PVC), polypropylene, or high-density polypropylene, which is designed to resist tearing and puncturing that may be encountered during normal operation. The sealable material can be selected to be transparent for visual inspection of the biological material within the flexible container 111 and can be provided in a variety of specifications, for example, ranging from about 10 mL to about 10 L.

[0062] The tray assembly 100 can be made of a variety of materials. For example, the lid 102, the tray 104, the leg members 114, and / or the partition 108 can comprise stainless steel (such as 316 stainless steel). Other metals or alloys can also be used, provided that the materials can withstand the temperatures and pressures associated with the freeze-drying process. The sealing member 112 can comprise silicone rubber (such as 70D silicone rubber) or one or more other or alternative compressible materials.

[0063] Figure 1B A plan view of the tray assembly 100 with the lid 102 attached to the tray 104 is shown. As shown, the perimeter of the lid 102 can be rectangular or approximately rectangular, while the perimeter wall 110 of the tray 104 can comprise a rounded corner portion 116 that matches the rounded corners of the sealing member 112. The shape of the lid 102 and / or the tray 104 can vary. In other embodiments, the lid and / or the tray can be, for example, approximately square, rectangular, oval, circular, irregular, or other shapes.

[0064] The planar dimensions of the lid 102 can be slightly larger than the planar dimensions of the tray 104, so that the lid does not fit inside the tray 104 but is placed on top of the perimeter wall 110 defined by the tray 104. When the lid 102 is coupled to the tray 104, a portion of the lid 102 can extend beyond at least a portion of the perimeter of the tray 104 to form an overhang, which can facilitate manually removing the lid 102 from the tray 104. The leg members 114 can be positioned near the perimeter edge of the lid and offset from the rounded corners. The illustrated example includes four leg members 114, which are positioned near the side 110b of the perimeter wall 110 and offset from the end 110a. Other embodiments can include fewer or more legs, such as one, two, three, five, six, seven, eight, or more legs.

[0065] Figure 1C A side view of the tray assembly 100 in an open configuration is shown, with a gap 118 between the lid 102 and the tray 104. This gap 118 allows air and solvent vapor to be released from the container 111 placed in the cavity 106 of the tray 104 during the freeze-drying process. In the open configuration, the leg members 114 can be held in an extended position such that the stable support base 120 of the lower telescoping portion 122 of each leg member 114 abuts against the bottom of the tray 104, but the lower telescoping portion 122 is not fully retracted into the upper portion 124.

[0066] In Figure 1CIn the specific embodiment shown, the lower telescoping portion 122 includes an elongate shaft or a locating pin member configured to be slidably received within the upper portion 124, which defines a complementary tubular member. Examples of the locating pin member can include a ball-head locating pin (e.g., having one, two, three, or more ball-head members) configured to be received within one or more lateral cavities or circumferential grooves defined by the inner surface of the upper portion 124. In some examples, the inner surface of the upper portion 124 can define a single lateral cavity or circumferential groove (e.g., near the lower end of the upper portion 124), where the reversible engagement of a locating member (such as a ball-head) protruding from the lower telescoping portion 122 with this groove can lock the leg member 114 in the extended configuration. In other embodiments, the upper portion 124 can define separate circumferential grooves spaced along the longitudinal axis of the upper portion 124 such that one or more grooves are defined near the first (lower) end of the upper portion 124 and another or more grooves are located near the second (upper) end of the upper portion 124. The locking engagement of the locating member with the groove defined near the lower end of the upper portion 124 can fix the tray assembly 100 in the open configuration, while the locking engagement of the locating member with the groove defined near the upper end of the upper portion 124 can fix the tray assembly 100 in the closed configuration. By pushing the ball-head members out of their respective receiving grooves, the tray assembly can be unlocked to switch between the two configurations. Specifically, transitioning from the open configuration to the closed configuration may involve applying sufficient downward force to move the locating member out of its corresponding groove (as described below in connection with the movable freeze-dryer shelf). Transitioning from the closed configuration to the open configuration may involve applying a force of equal or greater magnitude in the opposite direction. Additional adjustment mechanisms or components (such as other positioning components or springs) can be utilized to reversibly increase and decrease the length of the leg member 114 and lock the leg member 114 in the open and / or closed configurations. In some embodiments, for example, the leg member 114 can be biased towards the open configuration. According to such embodiments, only one end (such as the upper end) of the upper portion 124 can define a lateral groove configured to receive the locating member of the lower telescoping portion 122. In some examples, the leg member 114 can be temporarily locked in the closed configuration to prevent accidental removal of the lid 102 and extend the allowed storage time. An additional locking mechanism can also be provided to fix the lid 102 to the tray 104.

[0067] In addition to the leg member 114, additional components, members, and / or mechanisms can be additionally or alternatively used to maintain the gap 118 between the lid 102 and the tray 104 until the freeze-drying process is complete, at which time these components, members, and / or mechanisms can be engaged or adjusted to close the lid 102 against the tray 104. Non-limiting examples of such components, members, and / or mechanisms can include one or more compressible drying foam components, collapsible members, and / or items that can be crushed or otherwise damaged when the lid 102 is pressed towards the tray 104.

[0068] Figure 1D Shown is an adjustable freeze dryer shelf 126 located above the tray assembly 100. The shelf 126 can be configured to apply pressure to the lid 102 when descending in the direction of the arrow, thereby pushing the lid 102 against the tray 104 and closing the gap 118 between the two components until a closed configuration is reached. The shelf 126 can descend after freeze drying is complete but before the dryer door is opened, such that steam is allowed to escape from the container 111 during freeze drying and then sealed to prevent contamination and exposure to ambient air, preferably before the tray assembly 100 is removed from the freeze drying chamber. The tray assembly 100 can remain in the closed configuration until transported to a controlled environment with a low risk of contamination, such as a sterile, low humidity environment. Subsequently, the tray assembly 100 can be opened and the container removed for further processing. The freeze drying chamber can contain multiple shelves 126, each configured to support at least one tray assembly 100, and at least one shelf configured to be raised and lowered to open and close the tray assembly, respectively. Shelf height adjustment can be achieved under the instruction of a computer controller.

[0069] In one example, the freeze dried biological material can be a plasma unit, which can contain about 250 to 270 milliliters or other amounts of plasma from a single donor. For example, the plasma unit can be dried to a moisture content of less than about 5% weight / weight (w / w) to be storable, transportable, subsequently reconstituted and applied to a subject. The moisture content of the dried plasma unit can vary, ranging from less than about 1% w / w to about 15% w / w, more than 15% w / w, or any value therebetween.

[0070] The freeze dried material sealed within the container 111 can be stored long - term. For example, the container 111 can maintain the freeze dried material in a moisture - free environment prior to reconstitution, enabling long - term storage (such as about two to three years at refrigerated temperatures or several months at room temperature) and maintaining its desired quality for infusion.

[0071] Figure 1E Shown is the bottom surface 102a of the lid 102, including four leg members 114, each leg member having an upper portion 124, a lower telescoping portion 122, and a support base 120.

[0072] Figures 2A to 2E Shown are the various components of a tray assembly (such as tray assembly 100), and non - limiting example dimensions of each component according to various embodiments disclosed herein.

[0073] Figure 2Ais a plan view of tray 204, which shows separator 208 spanning side 210b of peripheral wall 210. In the illustrated example, the distance D1 between left end 210a and the nearest separator 208 is about 5.8 inches (±0.25 inches), and the same is true for the distance D2 between adjacent separators 208. The distance between separators 208 (and between separator 208 and adjacent end 210a) can vary and, in various non-limiting examples, ranges from about 3 inches to about 3.5 inches, to about 4.0 inches, to about 4.5 inches, to about 5.0 inches, to about 5.5 inches, to about 6.0 inches, to about 6.5 inches, to about 7.0 inches, to about 7.5 inches, to about 8.0 inches, to about 8.5 inches, to about 9.0 inches, to about 9.5 inches, to about 10 inches or greater. In some examples, the position of one or more separators 208 can be adjusted to accommodate containers of various different sizes and shapes.

[0074] Cross-section A-A and detail A show that the intersection of the top 208t of separator 208 and side 210b of peripheral wall 210 (the upper part of side 210b is marked as 210t) can form an angle of approximately 90°. Other suitable configurations can also be used. Detail A shows cutout 208c of separator 208 defined near upper part 210t of peripheral wall 210. Cutout 208c can be configured to accommodate a sealing member (such as sealing member 112).

[0075] Figure 2B Shows tray 204 without any separators. In a particular embodiment, the width WT of tray 204 is about 13.25 inches (±0.1 inch), and in other non-limiting embodiments, it ranges from about 8 inches to about 8.5 inches, to about 9.0 inches, to about 9.5 inches, to about 10.0 inches, to about 10.5 inches, to about 11.0 inches, to about 11.5 inches, to about 12.0 inches, to about 12.5 inches, to about 13.0 inches, to about 13.5 inches, to about 14.0 inches, to about 14.5 inches, to about 15.0 inches, to about 15.5 inches, to about 16.0 inches, to about 16.5 inches, to about 17.0 inches, to about 17.5 inches, to about 18.0 inches, to about 18.5 inches, to about 19.0 inches, to about 19.5 inches, to about 20.0 inches or greater, or any width therebetween.

[0076] In a particular embodiment, the length LT of the tray 204 is about 29 inches. In other non-limiting embodiments, the length can range from about 20 inches to about 20.5 inches, to about 21.0 inches, to about 21.5 inches, to about 22.0 inches, to about 22.5 inches, to about 23.0 inches, to about 23.5 inches, to about 24.0 inches, to about 24.5 inches, to about 25.0 inches, to about 25.5 inches, to about 26.0 inches, to about 26.5 inches, to about 27.0 inches, to about 27.5 inches, to about 28.0 inches, to about 28.5 inches, to about 29.0 inches, to about 29.5 inches, to about 30.0 inches, to about 30.5 inches, to about 31.0 inches, to about 31.5 inches, to about 32.0 inches, to about 32.5 inches, to about 33.0 inches, to about 33.5 inches, to about 34.0 inches, to about 34.5 inches, to about 35.0 inches, to about 35.5 inches, to about 36.0 inches, to about 36.5 inches, to about 37.0 inches, to about 37.5 inches, to about 38.0 inches, to about 38.5 inches, to about 39.0 inches, to about 39.5 inches, to about 40.0 inches or greater, or any length therebetween.

[0077] In a particular embodiment, the height HT of the tray 204 is about 2.125 inches (±0.05 inches). In other non-limiting embodiments, the height can range from about 1.0 inches to about 1.5 inches, to about 2.0 inches, to about 2.5 inches, to about 3.0 inches, to about 3.5 inches, to about 4.0 inches, to about 4.5 inches, to about 5.0 inches or greater, or any height therebetween.

[0078] Figure 2C A front view of the separator 208 is shown. The length LD of the separator 208 can be slightly less than the width of the tray 204, for example, about 0.1 inches less in some examples. The height HD of the separator 208 can be slightly less than the height H of the tray 204, for example, about 0.1 inches less. The depth DC of the cutout can be between 0.25 inches and about 0.3 inches in non-limiting examples, and the width WC of the cutout can be between about 0.1 inches and about 0.15 inches in non-limiting examples.

[0079] Figure 2DShows various views of the cover 202. In a particular embodiment, the length LL of the cover 202 is approximately 30.0 inches. In other non - limiting embodiments, it ranges from approximately 20 inches to approximately 20.5 inches, to approximately 21.0 inches, to approximately 21.5 inches, to approximately 22.0 inches, to approximately 22.5 inches, to approximately 23.0 inches, to approximately 23.5 inches, to approximately 24.0 inches, to approximately 24.5 inches, to approximately 25.0 inches, to approximately 25.5 inches, to approximately 26.0 inches, to approximately 26.5 inches, to approximately 27.0 inches, to approximately 27.5 inches, to approximately 28.0 inches, to approximately 28.5 inches, to approximately 29.0 inches, to approximately 29.5 inches, to approximately 30.0 inches, to approximately 30.5 inches, to approximately 31.0 inches, to approximately 31.5 inches, to approximately 32.0 inches, to approximately 32.5 inches, to approximately 33.0 inches, to approximately 33.5 inches, to approximately 34.0 inches, to approximately 34.5 inches, to approximately 35.0 inches, to approximately 35.5 inches, to approximately 36.0 inches, to approximately 36.5 inches, to approximately 37.0 inches, to approximately 37.5 inches, to approximately 38.0 inches, to approximately 38.5 inches, to approximately 39.0 inches, to approximately 39.5 inches, to approximately 40.0 inches, to approximately 40.5 inches, to approximately 41.0 inches or greater, or any length therebetween.

[0080] In a particular embodiment, the width WL of the cover 202 is approximately 13.8 inches. In other non - limiting embodiments, it ranges from approximately 8 inches to approximately 8.5 inches, to approximately 9.0 inches, to approximately 9.5 inches, to approximately 10.0 inches, to approximately 10.5 inches, to approximately 11.0 inches, to approximately 11.5 inches, to approximately 12.0 inches, to approximately 12.5 inches, to approximately 13.0 inches, to approximately 13.5 inches, to approximately 14.0 inches, to approximately 14.5 inches, to approximately 15.0 inches, to approximately 15.5 inches, to approximately 16.0 inches, to approximately 16.5 inches, to approximately 17.0 inches, to approximately 17.5 inches, to approximately 18.0 inches, to approximately 18.5 inches, to approximately 19.0 inches, to approximately 19.5 inches, to approximately 20.0 inches, to approximately 20.5 inches, to approximately 21 inches, to approximately 21.5 inches, to approximately 22.0 inches or greater, or any width therebetween.

[0081] As shown in detail B and cross - section B - B, the periphery of the cover 202 may include an overhang 212, which may facilitate manual grasping of the cover 202 and the coupling between the cover 202 and a sealing member (such as sealing member 112).

[0082] Figure 2EShows a compressible component in the form of a leg member component 214 (such as the upper part 124 of the leg member component 114). As shown, the leg member component 214 includes a circumferential inner groove 216, which is designed and configured to receive a positioning member (such as a positioning ball) or a similar component protruding from the side of a positioning pin member (such as the lower part 122 of the leg member 114). As shown in cross-section C-C, in a particular embodiment, the diameter DS of the inner groove 216 is about 0.3 inches, and in other non-limiting examples, it ranges from about 0.1 inches to about 0.5 inches. In a particular embodiment, the length LS of the inner groove 216 is about 0.065 inches, and in other non-limiting examples, it ranges from about 0.05 inches to about 0.1 inches.

[0083] In a particular embodiment, the length LLM of the leg member component 214 is about 1.9 inches, and in other non-limiting examples, it ranges from about 1.0 inches to about 4.0 inches. In a particular embodiment, the outer diameter OD of the leg member component 214 is about 0.5 inches, and in other non-limiting examples, it ranges from about 0.25 inches to about 1.0 inches. In a particular embodiment, the inner diameter ID of the leg member component 214 is about 0.25 inches, and in other non-limiting embodiments, it ranges from about 0.15 inches to about 0.35 inches.

[0084] In some embodiments, the positions of one or more partition plates can be adjusted so that they are not parallel to each other, but at an angle or perpendicular. For example, Figure 3 Shows a tray 304, which includes two partition plates 308a and 308b arranged perpendicular to each other. In this configuration, the tray 304 thus includes three cavities 306a, 306b, 306c, and each cavity is configured to receive at least one container filled with a biological material.

[0085] Figure 4A Shows a tray assembly 400, which includes a lid 402, a tray 404, and a vent 406 including a Luer lock. The vent 406 can be an optional component and can be used to inject a gas (such as nitrogen or carbon dioxide), or allow air to enter to relieve the vacuum seal between the lid and the tray. Figure 4B Shows a close-up view of the vent 406 protruding from the outer surface of the tray 404.

[0086] The disclosed tray assembly and related methods of use may be crucial for providing first aid to a subject suffering from severe injuries (such as wounds caused in an accident or a military operation). Although treating the wound and stopping the bleeding of the subject is necessary, it is equally important to ensure that the subject's body can function properly. Therefore, it is necessary to take measures to ensure that the subject's body can be properly hydrated after fluid loss due to blood loss from the wound.

[0087] When using the prior art, body fluids in a subject are typically replenished by intravenous infusion of saline. Although this method is effective, infusion of plasma into the subject is more effective in replenishing body fluids. The processing, storage, and delivery of plasma may be critical to prevent its contamination and maintain its desired physical properties. An effective way to deliver plasma is to store it in a lyophilized form and reconstitute it when administered to the subject.

[0088] The advantage of lyophilized materials is that they can be stored for a relatively long period at about 0 °C (degrees Celsius) to room temperature or even higher temperatures, and their weight is also reduced due to the decreased water content. Although lyophilized materials need to be reconstituted, their advantages are significant in some cases, especially in emergency medicine under difficult treatment conditions (such as treating injured soldiers on the battlefield or handling civilian trauma in ambulances and helicopters), where thawing frozen biological materials to be administered is both time-consuming (such as about 15 minutes or longer) and inconvenient.

[0089] Figure 5 A method 500 is shown, which includes filling a container with a biological material (such as plasma), inserting the filled container into a tray of a tray assembly, lyophilizing the biological material in the tray assembly, and removing the plasma from the lyophilization chamber without the risk of contamination and exposure to ambient air.

[0090] In operation 502, a plasma source unit can be obtained. Plasma can be obtained from a single donor or pooled from multiple donors: whole blood units from donors are collected in a closed-system collection bag, and then the plasma is separated by centrifugation and collected in an integrally connected transfer bag. For example, plasma can be obtained in units of about 270 mL, frozen and transported, and stored in a freezer at 20 °C. Identification information saved by barcoding or other labeling methods can be provided with the plasma of each individual donor for traceability purposes.

[0091] In operation 504, the plasma source unit can be prepared for lyophilization. The plasma unit is removed from the freezer and any associated packaging is discarded. The plasma unit can be transferred to a plasma thawing device and thawed. For example, the thawed plasma unit can be barcode scanned and an identification label can be made, which can contain unit-specific information to maintain the traceability of the plasma.

[0092] In operation 506, the plasma can be transferred to the container described herein. In some embodiments, the container can be a flexible, impermeable, breathable, sterile, and sealable container. The container and the plasma source unit can be connected using a material inlet in the form of a sterile catheter. The plasma can be transferred using positive pressure through the sterile catheter, and the total mass of the transferred plasma is about 270 g. After the plasma transfer is complete, a portion of the sterile catheter can be heat-sealed or otherwise sealed to protect the unit from contamination and exposure to ambient air.

[0093] In operation 508, a filled container can be placed in the cavity of a horizontally oriented freeze dryer tray. In operation 510, a lid can be placed above the tray without sealing the lid against the tray, such that a horizontal gap exists between the bottom surface of the lid and the upper edge of the tray. Subsequently, in operation 512, the open tray assembly is placed on a shelf in the freeze dryer chamber and freeze drying is performed. When the tray assembly is in the open state, the container is freeze dried. Since air or solvent vapor can escape from the container through a membrane or the like and can also escape from the tray assembly through the gap between the lid and the tray, controlled and consistent conduction can be achieved during the freeze drying process.

[0094] Freeze drying can include using a heating and cooling device to cool the shelf to initially freeze the material to be freeze dried. Alternatively, a separate unit (such as a -60 °C freezer) can be used to pre-freeze the filled containers to be freeze dried and arranged on the shelf. The solvent vapor released by the sublimation of the material in the container can be captured by a cold trap or other types of trapping devices. In the case of using a cold trap (condenser device), the cold trap can be cooled to a temperature lower than the temperature of the material, preferably to a temperature at which the solvent vapor pressure is significantly lower than the vapor pressure of water at the temperature of the contents (e.g., -50 to -60 °C).

[0095] In one example, the freeze drying cycle can include cooling the shelf to below about -40 °C, loading the filled container and its tray onto the shelf, initiating a six- or seven-day freeze drying cycle (including a four- or five-day primary drying cycle and a two-day secondary drying cycle), ending the secondary drying cycle and breaking the vacuum using ultra-dry high-purity carbon dioxide.

[0096] In operation 514, the tray assembly can be closed by lowering the shelf directly above the tray assembly onto the lid and pushing the lid downward (through the leg members of the compression assembly) until it seals against the upper edge of the tray. In this closed configuration, the tray assembly can be removed from the freeze drying chamber and transferred to a sterile environment (such as a dry storage room) in operation 516. Subsequently, the tray assembly can be opened in operation 518 and the container can be removed therefrom. The tray assembly can be reused after sterilization.

[0097] Figure 5 The order of steps shown can be adjusted as needed.

[0098] Conclusion

[0099] Existing components, systems, and methods for freeze-drying, repackaging, and using freeze-dried contents suffer from problems of contamination, cost, and lack of convenience. Advantageously, the present application provides a cost-effective component, system, and method for protecting materials from contamination and unnecessary alteration through steps such as filling, freeze-drying, packaging, storing, and using. The component, system, and method can be designed for blood products, such as plasma, and can be applicable to other materials that benefit from the design and features of the present application.

[0100] The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The accompanying drawings should be referred to when reading the detailed description. The accompanying drawings illustrate specific embodiments of the components, systems, and related methods of the present application in an illustrative manner. These embodiments are also referred to herein as "examples".

[0101] The detailed description is intended to be illustrative and not restrictive. For example, the above examples (or one or more features or components thereof) may be used in combination with each other. Those skilled in the art may use other embodiments when reviewing the above detailed description. In addition, various features or components have been grouped together or may be grouped together to simplify the present disclosure. This should not be construed as intending that the unclaimed disclosed features are essential to any claim. Instead, the subject matter of the present application may lie in less than all of the features of the specifically disclosed embodiments. Accordingly, the following claim examples are hereby incorporated into the detailed description, where each example stands alone as a separate embodiment:

[0102] Certain terms are used throughout this application to refer to particular features or components. As will be understood by those skilled in the art, different people may refer to the same feature or component by different names. This application is not intended to distinguish between components or features that have different names but different functions.

[0103] For the terms defined below, certain definitions shall apply unless a different definition is given elsewhere in this application. The terms "a", "an", and "the" are used to include one or more than one, independent of any other instances or uses of "at least one" or "one or more". The term "or" is used to mean a non-exclusive or, such that "A or B" includes "A but not B", "B but not A", and "A and B". It is assumed that all numerical values are modified by the term "about", whether or not explicitly stated. The term "about" generally means a numerical range that a person skilled in the art would consider equal to the recited value (e.g., having the same function or result). In many instances, the term "about" may include numbers rounded to the nearest significant digit. A numerical range recited by endpoints includes all numbers and sub-ranges within that range and defining that range (e.g., 1 to 4 includes 1, 1.5, 1.75, 2, 2.3, 2.6, 2.9, etc. and 1 to 1.5, 1 to 2, 1 to 3, 2 to 3.5, 2 to 4, 3 to 4, etc.). The terms "patient" and "subject" are intended to include mammals, such as for human or veterinary applications.

[0104] The scope of this application shall be determined with reference to the appended claims and the full scope of the equivalents thereto. In the appended claims, the terms "comprising" and "wherein" are used as the plain English equivalents of the corresponding terms "including" and "wherein". Also, in the following claims, the terms "comprising" and "containing" are open-ended; i.e., an assembly, system, or method that includes features or components other than those listed after such terms in the claims is still considered to fall within the scope of that claim. Also, in the following claims, the terms "first", "second", "third", etc. are used only as labels and are not intended to impose numerical requirements on their objects.

[0105] The abstract is provided to enable the reader to quickly ascertain the essence of the technical disclosure. It should be understood that when submitting this abstract, it shall not be used to interpret or limit the scope and meaning of the claims.

Claims

1. A freeze-drying tray assembly, comprising: A tray configured to accommodate one or more containers, each of the one or more containers containing a liquid; And A lid complementary to the tray and including one or more compressible members configured to transition from an extended configuration to a compressed configuration in response to a downward force applied to the lid when the lid is positioned above the tray; Wherein, when the one or more compressible members are in the extended configuration, there is a gap between the upper edge of the tray and the bottom surface of the lid, and Wherein, when the one or more compressible members are in the compressed configuration, the lid seals against the upper edge of the tray.

2. The tray assembly according to claim 1, further comprising a gasket attached to the upper edge of the tray.

3. The tray assembly according to claim 1, wherein, The tray includes one or more partition plates configured to define two or more cavities within the tray, each cavity configured to accommodate at least one container.

4. The tray assembly according to claim 3, wherein the partition plates are movable within the tray.

5. The tray assembly according to claim 1, wherein, Each of the compressible members includes a compressible leg member having a first portion and a second portion, the first portion being movable relative to the second portion.

6. The tray assembly according to claim 5, wherein, The first portion includes a telescopic positioning pin member.

7. The tray assembly according to claim 6, wherein, The second portion includes a tubular member configured to accommodate the telescopic positioning pin member.

8. The tray assembly according to claim 7, wherein, The tubular member is attached to the bottom surface of the lid, and the telescopic positioning pin member is configured to extend to the inner bottom surface of the tray.

9. The tray assembly according to claim 8, wherein, The support base of the telescopic positioning pin member is configured to contact the inner bottom surface of the tray.

10. The tray assembly according to claim 1, wherein, The tray and the lid are made of stainless steel.

11. The tray assembly according to claim 1, further comprising a vent attached to the tray.

12. The tray assembly according to claim 1, wherein, The tray has a length of about 20 inches to about 40 inches.

13. The tray assembly according to claim 1, wherein, The tray has a width of about 8 inches to about 20 inches.

14. The tray assembly according to claim 1, wherein, The tray has a height of about 1 inch to about 5 inches.

15. A system for freeze-drying biological materials, comprising: At least one airtight container configured to accommodate biological materials; And A tray assembly configured to accommodate the at least one airtight container, the tray assembly including: A tray configured to accommodate the at least one airtight container; and A lid complementary to the tray and including one or more compressible members configured to transition from an extended configuration to a compressed configuration in response to a downward force applied to the lid when the lid is positioned above the tray; Wherein, when the one or more compressible members are in the extended configuration, there is a gap between the upper edge of the tray and the bottom surface of the lid, and Wherein, when the one or more compressible members are in the compressed configuration, the lid seals against the upper edge of the tray.

16. The system according to claim 15, further comprising a movable freeze-dryer shelf.

17. The system according to claim 16, wherein, The movable freeze-dryer shelf is configured to apply a downward force sufficient to seal the lid against the upper edge of the tray.

18. The system according to claim 15, wherein, The tray assembly further includes a vent.

19. The system according to claim 15, wherein The biological material includes plasma.

20. The system according to claim 15, wherein Each of the one or more compressible members includes a compressible leg member.

Images